肌萎缩性侧索硬化症神经退行性变的分子生物标志物

IF 2.3 4区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY
Denis V. Shevchuk, Amir I. Tukhvatulin, Alina S. Dzharullaeva, Irina A. Berdalina, Maria N. Zakharova
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引用次数: 0

摘要

肌萎缩侧索硬化症(ALS)是最常见的运动神经元疾病。然而,由于缺乏特异性和敏感的ALS生物标志物,最终诊断可能会延迟长达12个月。在我们的研究中,我们首次在俄罗斯人群中对大型ALS患者队列(n = 100)进行了研究,我们评估了神经退行性病理的关键生物标志物,包括β-淀粉样蛋白(a β40和a β42)和tau蛋白(tau -total和tau -p181),以及其他与病理相关的有前景的生物标志物,如FGF-21、Kallikrein-6 (KLK-6)、nam -1、Neurogranin (NRGN)、TDP-43、载脂蛋白E4、Clusterin (Apo J)、补体因子H、Fetuin-A、α2-Macroglobulin、Apo AI、Apo CIII, Apo E,补体C3, GDNF, sRAGE和S100B蛋白。ALS患者与对照组Aβ40 (p = 0.044)、Aβ42 (p <;0.001), FGF-21 (p <;0.001), Tau-total (p = 0.001), Tau-p181 (p = 0.014), Clusterin (p & lt;0.001),补体C3 (p = 0.001), S100B (p = 0.024)。ALSFRS-R评分与Aβ40和Aβ42浓度之间存在显著的直接相关。发现了补体系统(补体C3和补体因子H)的变化,强调了神经炎症过程在ALS发病机制中的关键作用。此外,在ALS患者中观察到FGF-21水平升高。在疾病快速进展的患者中,伴侣蛋白聚集蛋白的浓度显著增加,这表明它有可能作为运动神经元疾病的预后生物标志物。此外,它在维持蛋白质平衡中的作用可能提供新的治疗靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Molecular Biomarkers of Neurodegeneration in Amyotrophic Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is the most prevalent motor neuron disease. However, definitive diagnosis could be delayed by up to 12 months due to the lack of specific and sensitive biomarkers for ALS. In our study, conducted for the first time on a large cohort of ALS patients (n = 100) within the Russian population, we assessed key biomarkers of neurodegenerative pathology, including β-amyloids (Aβ40 and Aβ42) and tau proteins (Tau-total and Tau-p181), as well as other pathogenetically relevant, promising biomarkers such as FGF-21, Kallikrein-6 (KLK-6), NCAM-1, Neurogranin (NRGN), TDP-43, Apolipoprotein E4, Clusterin (Apo J), Complement Factor H, Fetuin-A, α2-Macroglobulin, Apo AI, Apo CIII, Apo E, Complement C3, GDNF, sRAGE, and S100B protein. Significant differences between the ALS patients and the control group were observed for Aβ40 (p = 0.044), Aβ42 (p < 0.001), FGF-21 (p < 0.001), Tau-total (p = 0.001), Tau-p181 (p = 0.014), Clusterin (p < 0.001), Complement C3 (p = 0.001), and S100B (p = 0.024). A significant direct correlation was found between the ALSFRS-R score and concentrations of Aβ40 and Aβ42. Changes in the complement system (Complement C3 and Complement Factor H) were identified, highlighting critical role of neuroinflammatory processes in ALS pathogenesis. Additionally, increased levels of FGF-21 were observed in the patients with the bulbar onset of ALS. Significant increase in the concentration of the chaperone protein clusterin in the patients with rapid disease progression suggests its potential as a prognostic biomarker for motor neuron disease. Furthermore, its role in maintaining proteostasis could provide novel therapeutic targets.

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来源期刊
Biochemistry (Moscow)
Biochemistry (Moscow) 生物-生化与分子生物学
CiteScore
4.70
自引率
3.60%
发文量
139
审稿时长
2 months
期刊介绍: Biochemistry (Moscow) is the journal that includes research papers in all fields of biochemistry as well as biochemical aspects of molecular biology, bioorganic chemistry, microbiology, immunology, physiology, and biomedical sciences. Coverage also extends to new experimental methods in biochemistry, theoretical contributions of biochemical importance, reviews of contemporary biochemical topics, and mini-reviews (News in Biochemistry).
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